Shake, Rattle and React: Proteins Dance across a Membrane

With a jiggle and a wiggle, proteins move through a layer of lipids similar to the membrane of a living cell. In a new study, researchers recorded these movements with unprecedented resolution, revealing how the molecules interact with one another. The results and short movie were published July 8 in Nature Nanotechnology. (Scientific American is part of Nature Publishing Group.)

The golden clusters in the image are porin proteins that commonly stud the outer membrane of Escherichia coli bacteria. These proteins allow small water molecules, ions, nutrients and waste to pass through. Each clump is actually three individual proteins hooked together to form a trimer (polymer). For this research, the team purified the proteins and seeded them at a realistic density in a sea of lipids to make a simple membrane.

Biology at the subcellular level can be likened to a dance: Proteins, lipids, sugars and other molecules follow specific steps to sustain the energy needs, respiration and reproduction of life. But before molecules boogie, they have to find the right partner. And partner availability determines when and how fast reactions happen. The crowding of proteins in a membrane helps them out: "The probability that you will meet a partner is greater than if you are alone in the street," says lead author Simon Scheuring, a biologist at Aix–Marseille University in France. His team found that happily partnered molecules don't move through the membrane much. Meanwhile, the uncoupled molecules continue to jostle around in search of a good interaction.

To peer into this tiny world, Scheuring's team uses high-speed atomic force microscopy, which works like an old record player. A tip only a couple nanometers in diameter scans the surface of a sample. The tip is attached to a cantilever, and a laser spot tracks the motion of the arm as it judders over minuscule bumps and valleys. Until recently, acquiring one image with this technology took as long as two minutes. With lighter, smaller instrument components and faster electronics, researchers can now capture about 10 frames per second.